19-19297055-T-C

Position:

• chr19-19297055-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172231.4(SUGP1):​c.1177A>G​(p.Lys393Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SUGP1 NM_172231.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

Genes affected

SUGP1 (HGNC:18643): (SURP and G-patch domain containing 1) SF4 is a member of the SURP family of splicing factors.[supplied by OMIM, Sep 2003]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SUGP1	NM_172231.4	c.1177A>G	p.Lys393Glu	missense_variant	8/14	ENST00000247001.10	NP_757386.2
SUGP1	XM_047439142.1	c.547A>G	p.Lys183Glu	missense_variant	6/12		XP_047295098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SUGP1	ENST00000247001.10	c.1177A>G	p.Lys393Glu	missense_variant	8/14	1	NM_172231.4	ENSP00000247001	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250854 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135586

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460422 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726434

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.1177A>G (p.K393E) alteration is located in exon 8 (coding exon 8) of the SUGP1 gene. This alteration results from a A to G substitution at nucleotide position 1177, causing the lysine (K) at amino acid position 393 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.047	D
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.68
MutPred		0.21		Loss of ubiquitination at K393 (P = 0.0037);
MVP		0.13
MPC		0.96
ClinPred		0.92	D
GERP RS		3.7
Varity_R		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs750287204; hg19: chr19-19407864;